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2q1r

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Crystal Structure Analysis of the RNA Dodecamer CGCGAAUUAGCG, with a G-A mismatch.

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Retrieved from "http://52.214.119.220/wiki/index.php/2q1r"

Categories: Large Structures | Li F | Pallan PS

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-[[Image:2q1r.gif|left|200px]]<br /><applet load="2q1r" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2q1r, resolution 1.12&Aring;" />
-'''Crystal Structure Analysis of the RNA Dodecamer CGCGAAUUAGCG, with a G-A mismatch.'''<br />
-==Overview==
+==Crystal Structure Analysis of the RNA Dodecamer CGCGAAUUAGCG, with a G-A mismatch.==
-Short interfering RNA (siRNA) duplexes are currently being evaluated as, antisense agents for gene silencing. Chemical modification of siRNAs is, widely expected to be required for therapeutic applications in order to, improve delivery, biostability and pharmacokinetic properties. Beyond, potential improvements in the efficacy of oligoribonucleotides, chemical, modification may also provide insight into the mechanism of mRNA, downregulation mediated by the RNA-protein effector complexes (RNA-induced, silencing complex or RISC). We have studied the in vitro activity in HeLa, cells of siRNA duplexes against firefly luciferase with substitutions in, the guide strand of U for the apolar ribo-2,4-difluorotoluyl nucleotide, (rF) [Xia, J. et al. (2006) ACS Chem. Biol., 1, 176-183] as well as of C, for rF. Whereas an internal rF:A pair adjacent to the Ago2 ('slicer', enzyme) cleavage site did not affect silencing relative to the native, siRNA duplex, the rF:G pair and other mismatches such as A:G or A:A were, not tolerated. The crystal structure at atomic resolution determined for, an RNA dodecamer duplex with rF opposite G manifests only minor deviations, between the geometries of rF:G and the native U:G wobble pair. This is in, contrast to the previously found, significant deviations between the, geometries of rF:A and U:A pairs. Comparison between the structures of the, RNA duplex containing rF:G and a new structure of an RNA with A:G, mismatches with the structures of standard Watson-Crick pairs in canonical, duplex RNA leads to the conclusion that local widening of the duplex, formed by the siRNA guide strand and the targeted region of mRNA is the, most likely reason for the intolerance of human Ago2 (hAgo2), the RISC, endonuclease, toward internal mismatch pairs involving native or, chemically modified RNA. Contrary to the influence of shape, the, thermodynamic stabilities of siRNA duplexes with single rF:A, A:A, G:A or, C:A (instead of U:A) or rF:G pairs (instead of C:G) show no obvious, correlation with their activities. However, incorporation of three rF:A, pairs into an siRNA duplex leads to loss of activity. Our structural and, stability data also shed light on the role of organic fluorine as a, hydrogen bond acceptor. Accordingly, UV melting (T(M)) data, osmotic, stress measurements, X-ray crystallography at atomic resolution and the, results of semi-empirical calculations are all consistent with the, existence of weak hydrogen bonds between fluorine and the H-N1(G) amino, group in rF:G pairs of the investigated RNA dodecamers.
+<StructureSection load='2q1r' size='340' side='right'caption='[[2q1r]], [[Resolution|resolution]] 1.12&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[2q1r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q1R FirstGlance]. <br>
-Q1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1R OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.12&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1r OCA], [https://pdbe.org/2q1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q1r RCSB], [https://www.ebi.ac.uk/pdbsum/2q1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q1r ProSAT]</span></td></tr>
-Crystal structure, stability and in vitro RNAi activity of oligoribonucleotides containing the ribo-difluorotoluyl nucleotide: insights into substrate requirements by the human RISC Ago2 enzyme., Li F, Pallan PS, Maier MA, Rajeev KG, Mathieu SL, Kreutz C, Fan Y, Sanghvi J, Micura R, Rozners E, Manoharan M, Egli M, Nucleic Acids Res. 2007 Sep 18;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17881374 17881374]
+</table>
-[[Category: Single protein]]
+__TOC__
-[[Category: Li, F.]]
+</StructureSection>
-[[Category: Pallan, P.S.]]
+[[Category: Large Structures]]
-[[Category: MG]]
+[[Category: Li F]]
-[[Category: g-a mismatch]]
+[[Category: Pallan PS]]
-[[Category: rna]]
-[[Category: rnai]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:40:27 2008''

2q1r

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Crystal Structure Analysis of the RNA Dodecamer CGCGAAUUAGCG, with a G-A mismatch.

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